This project is a continuation of an investigation into regulation of intermediary metabolism in the kidney by acid-base homeostasis. The emphasis in the project is to relate properties of the inner mitochrondrial membrane to two different metabolic responses by the kidney to alterations in acid-base balance. (1) Levels in renal cortex of a number of citric acid cycle and related su strates decrease in acute metabolic acidosis and increase in metabolic alkalosis. We postulate that these changes are the result of substrate shifts occurring in response to variations in the mitochondrial pH gradient. Studies will be carried out in isolated kidney tubules and in mitochondria to determine the validity of this hypothesis. (2) During chronic metabolic acidosis renal ammoniagenesis from glutamine increases strikingly. Previous work has suggested that a major factor in this adaptive response is an increase in acidosis in glutamine transport by its carrier in the inner mitochondrial membrane, leading to delivery of more glutamine to phosphate dependent glutaminase. Further evidence for adaptation of the glutamine transporter in acidosis will be sought in studies on mitochondria and inner membrane vesicles.